BA

• The three ways netrophils can destroy an infectious agent: by capture and destroy invading microorganisms, through phagocytosis and intracellular degradation, release of granules, and formation of neutrophil extracellular traps after detecting pathogens.
• The primary lymphatic organs are the bone marrow and the thymus, which are responsible for producing and maturing lymphocytes, or immune system cells:
• Secondary lymphoid organs: These organs include the lymph nodes, the spleen, the tonsils and certain tissue in various mucous membrane layers in the body
• Antibody structure

  A) light

  B) heavy

  C) disulfide

  D) antigen binding site

  E) hinge region

  F) effector region

  G)

  
• A heavy chain will have one Variable, one Diversity, one Joining and one Constant region
• A light chain will have one Variable, one Joining and one Constant region
• In the secondary lymphoid organs (e.g lymph node) the Dendritic Cell interacts with a CD4+ T-cell. The CD4+ T-cell has a T-cell receptor that binds to the MHC presenting the antigen and then the CD4+ T-cell proliferates.
• Class switch recombination (CSR) is a DNA rearrangement process that changes the type of immunoglobulin (Ig) produced by a B cell
• Class switch recombination (CSR) allows for the expression of antibodies that have the same antigen but are of a secondary isotype (IgG, IgA or IgE) and thereby have a different effector function.
• IgA binds to pathogens to tag them for destruction by other antibodies.
•  IgG protects against bacterial and viral infections by binding to pathogens and alerting other immune cells to attack them.
• IgM is the first antibody the body produces when it fights a new infection. It also serves as a memory bank for the immune system
• IgE is responsible for allergic reactions. It binds to allergens, triggering mast cells to release histamine and other chemicals into the bloodstream
• IgD binds to B cells to kick start the immune response. It may also act as an anti-inflammatory, preventing allergic reactions, and protecting the body from autoimmune diseases and severe infections
• Somatic hypermutation (SHM)

  Alters the affinity of antibodies by introducing mutations in the V region of the heavy and light chains. This process allows B cells to be selected that produce antibodies with increased antigen affinity.
• Class switch recombination (CSR)

  Modifies the effector activity of antibodies by replacing the initial heavy-chain C regions with another isotype. This process produces different isotypes and subclasses with different functional properties
• B cells work with other cells in your immune system to fight harmful invaders that can make you sick and abnormal cells, like cancer cells. Once B cells are activated, they become plasma cells that produce antibodies in response to an antigen.
• A hypersensitivity reaction is an inappropriate or exaggerated response to an antigen or an allergen.
• Mast cells act like an alert system. They protect your body from foreign invaders (pathogens like viruses, bacteria and parasites) and toxins (for instance, venom from snake bites or bee stings). They also fight off particles they think are harmful, even when they're not. This causes allergic reactions.
• Histamines are one type of mediator released by your mast cells during the inflammatory immune response to allergens. In a healthy individual, these mediators help protect and heal your body. Mast cell activation syndrome, on the other hand, is when histamines are in hyperdrive.
• Mast cells are now thought to exert critical proinflammatory functions, as well as potential immunoregulatory roles, in various immune disorders through the release of mediators such as histamine, leukotrienes, cytokines chemokines, and neutral proteases
• A mast cell is a resident cell of connective tissue that contains many granules rich in histamine and heparin. It is a type of granulocyte derived from the myeloid stem cell.
• IgE elicits an immune response by binding to Fc receptors found on the surface of mast cells and basophils, and are also found on eosinophils, monocytes, macrophages and platelets in humans.
• IgE binds to Fc epsilon receptors on mast cells to trigger their activation
• Stages of allergy:

  • The first time someone encounters a potential allergen, they will produce large amounts of IgE antibody
  • This IgE molecules attach to mast cells, priming them.
  • The next time someone encounters the allergen the primed mast cells actions will be triggered.
  • And symptoms of allergy will be triggered
• Some of the symptoms of an allergic reaction include:

  • Itchy eyes.
  • Itchy nose.
  • Sneezing.
  • Runny nose.
  • Rashes.
  • Hives
  • Stomach cramps.
  • Vomiting.
• • AnaphylaxisA life-threatening emergency that usually begins within minutes of exposure to an allergen: 
  • Swelling of the throat or tongue 
  • Difficulty breathing or breathing very fast 
  • Wheezing, coughing, or noisy breathing 
  • Feeling faint, dizzy, or fainting 
  • Skin that feels cold to the touch 
  • Blue, gray, or pale skin, lips, or tongue 
• The proteasome is an essential part of our immune surveillance mechanisms: by generating peptides from intracellular antigens it provides peptides that are then 'presented' to T cells.
• Type I hypersensitivity is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen.
• Stages of type 1 hypersensitivity:

  • First exposure to allergen - an APC will process allergen and present antigen to T Helper cell
  • T Helper cell releases IL-4 and IL-12 and binds to B-Cell activating it
  • B cells proliferate and differentiate into plasma cells that will secrete IgE
  • IgE binds to Fc epsilon regions on mast cells, sensitising them
  • Upon subsequent exposure mast cells with IgE bind to allergen and release antiinflammatory molecules, resulting in allergy symptoms.
• Allergy Mediators Produced by Mast Cells

  A) Vascular dilation

  B) Tissue Damage

  C) Vascular dilation

  D) Contraction

  E) Inflammation

  
• Allergy Mediators Produced by Mast Cells

  A) vasoactive amines such as histamine

  B) Proteases

  C) prostaglandins

  D) leukotrienes

  E) Cytokines

  
• Mast cell degranulation triggers inflammation, which recruits basophils and eosinophils
• The immediate allergic reaction caused by mast-cell degranulation is followed by more sustained inflammation known as late-phase response. The late response involves recruitment of other effector cells: Th2 lymphocytes, eosinophils and basophils.
• Allergic response immediate phase:

  • Within seconds
  • Preformed mediators: histamine, prostaglandins.
  • Increase in vascular permeability, contraction of smooth muscle.
• Allergic response late phase phase:

  • 8-12 hours to develop
  • Synthesis and release of mediators: prostaglandins, leukotrienes, chemokines, cytokines from activated mast cells.
  • Recruitment of other leukocytes: eosinophils, Th2 lymphocytes.
  • Edema and tissue remodeling including smooth muscle hypertrophy and hyperplasia
• When mast cells are activated in the heart and vascular system, they can trigger increased permeability and entry of fluid into the tissues. Swelling of tissues, including the tongue, loss of blood pressure, reduced oxygen to tissues, irregular heartbeat, anafalatick shock and loss of consciousness.
• When mast cells are triggered in the respiratory tract, they can trigger contraction of smooth muscle and constriction of throat and airways. Difficulty in swallowing and breathing as well as wheezing.
• When mast cells are triggered in the gastrointestinal track, they can trigger contraction of smooth muscle, stomach cramps, vomiting, fluid outflow and diarrhoea.
• IgE mediated Responses Defend against Multicellular Parasites

  • IgE is involved in protective immunity (parasitic worms in developing countries).
  • Parasites are large multicellular organisms and are not readily killed by macrophages or neutrophils
  • Cross linking of IgE on mast cells leads to mast cell degranulation  which leads to a response that results in the dislodging of the parasite
  • These reactions rarely eradicate the parasite but reduce its population size and reduce disease